tbuckley/cabot-search huggingface dataset:
Corrigendum to “Degradation of 3D-printed magnesium phosphate ceramics in vitro and a prognosis on their bone regeneration potential” [Bioact. Mater. 19 (2023) 376–391/22]
Authors: Eugen Gefel, Claus Moseke, Anna-Maria Schmitt, Niklas Dümmler, Philipp Stahlhut, Andrea Ewald, Andrea Meyer-Lindenberg, Elke Vorndran
Journal: Bioactive Materials (2022)

[This corrects the article DOI: 10.1016/j.bioactmat.2022.04.015.].
The importance of ecological validity, ultimate causation, and natural categories
Authors: Catherine A. Salmon, Jessica A. Hehman
Journal: Behavioral and Brain Sciences (2022)

Abstract The target article raises important questions about the applicability of experimental social psychology research on topics with policy implications. This commentary focuses on the importance of attending to a variety of factors to improve ecological validity as well as considering the ultimate factors shaping behavior and the role of natural categories in the stability of stereotypes and their influence.
<scp>Multi‐variable</scp> biomarker approach in identifying incident heart failure in chronic kidney disease: results from the Chronic Renal Insufficiency Cohort study
Authors: Scott E. Janus, Jamal Hajjari, Tarek Chami, Haytham Mously, Anshul K. Badhwar, Mohamad Karnib, Herman Carneiro, Mahboob Rahman, Sadeer G. Al‐Kindi
Journal: European Journal of Heart Failure (2022)
Evaluation of a Gene–Environment Interaction of <i>PON1</i> and Low-Level Nerve Agent Exposure with Gulf War Illness: A Prevalence Case–Control Study Drawn from the U.S. Military Health Survey’s National Population Sample
Authors: Robert W. Haley, Gerald Kramer, Junhui Xiao, Jill A. Dever, John F. Teiber
Journal: Environmental Health Perspectives (2022)

Background: Consensus on the etiology of 1991 Gulf War illness (GWI) has been limited by lack of objective individual-level environmental exposure information and assumed recall bias. Objectives: We investigated a prestated hypothesis of the association of GWI with a gene–environment (GxE) interaction of the paraoxonase-1 (PON1) Q192R polymorphism and low-level nerve agent exposure. Methods: A prevalence sample of 508 GWI cases and 508 nonpaired controls was drawn from the 8,020 participants in the U.S. Military Health Survey, a representative sample survey of military veterans who served during the Gulf War. The PON1 Q192R genotype was measured by real-time polymerase chain reaction (RT-PCR), and the serum Q and R isoenzyme activity levels were measured with PON1-specific substrates. Low-level nerve agent exposure was estimated by survey questions on having heard nerve agent alarms during deployment. Results: The GxE interaction of the Q192R genotype and hearing alarms was strongly associated with GWI on both the multiplicative [prevalence odds ratio (POR) of the interaction=3.41; 95% confidence interval (CI): 1.20, 9.72] and additive (synergy index=4.71; 95% CI: 1.82, 12.19) scales, adjusted for measured confounders. The Q192R genotype and the alarms variable were independent (adjusted POR in the controls=1.18; 95% CI: 0.81, 1.73; p=0.35), and the associations of GWI with the number of R alleles and quartiles of Q isoenzyme were monotonic. The adjusted relative excess risk due to interaction (aRERI) was 7.69 (95% CI: 2.71, 19.13). Substituting Q isoenzyme activity for the genotype in the analyses corroborated the findings. Sensitivity analyses suggested that recall bias had forced the estimate of the GxE interaction toward the null and that unmeasured confounding is unlikely to account for the findings. We found a GxE interaction involving the Q-correlated PON1 diazoxonase activity and a weak possible GxE involving the Khamisiyah plume model, but none involving the PON1 R isoenzyme activity, arylesterase activity, paraoxonase activity, butyrylcholinesterase genotypes or enzyme activity, or pyridostigmine. Discussion: Given gene–environment independence and monotonicity, the unconfounded aRERI>0 supports a mechanistic interaction. Together with the direct evidence of exposure to fallout from bombing of chemical weapon storage facilities and the extensive toxicologic evidence of biochemical protection from organophosphates by the Q isoenzyme, the findings provide strong evidence for an etiologic role of low-level nerve agent in GWI. https://doi.org/10.1289/EHP9009
Association of Congenital and Acquired Cardiovascular Conditions With COVID-19 Severity Among Pediatric Patients in the US
Authors: Louis Ehwerhemuepha, Bradley Roth, Anita K. Patel, Olivia Heutlinger, Carly Heffernan, Antonio C. Arrieta, Terence Sanger, Dan M. Cooper, Babak Shahbaba, Anthony C. Chang, William Feaster, Sharief Taraman, Hiroki Morizono, Rachel Marano
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Identifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment. <h3>Objective</h3> To assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021. <h3>Exposures</h3> Diagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2). <h3>Main Outcomes and Measures</h3> The main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure. <h3>Results</h3> The study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years. <h3>Conclusions and Relevance</h3> The findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.
Reverse Remodeling Assessed by Left Atrial and Ventricular Strain Reflects Treatment Response to Sacubitril/Valsartan
Authors: Mi-Gil Moon, In-Chang Hwang, Hyun-Jung Lee, Sun-Hwa Kim, Yeonyee E. Yoon, Jun-Bean Park, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim, Goo-Yeong Cho
Journal: JACC. Cardiovascular imaging (2022)
Clarification of Conflict of Interest Disclosures
Authors: Wayne Gao, Chi Wen, H Gilbert Welch
Journal: JAMA Internal Medicine (2022)

s Cancer Intervention and Surveillance Modeling Network model from the University of Michigan, for example, projects that the proportion of lung cancer deaths occurring in never smokers will rise from approximately 10% to more than 40% in the next 50 years, even while lung cancer incidence among never smokers remains stable. 5,6Complete success-a smoke-free world-will invariably mean that 100% of lung cancer deaths will be in never smokers.But the foregoing is not a rationale for screening never smokers.The reason to screen is to lower mortality, and there is no evidence that screening has this benefit in never smokers.As shown in our work, 1 however, there is evidence of obvious harm.Unless randomized clinical trials can demonstrate substantial benefit to low-risk groups, low-dose computed tomography screening should remain targeted only to heavy smokers.
Abstract B008: Man vs machine: Crowdsourcing vs deep learning of adaptive therapy strategies
Authors: Rafael R. Bravo, Brenden K. Peterson, Mark Robertson-Tessi, Daniel M. Faissol, Alexander R.A. Anderson
Journal: Cancer Research (2022)

Abstract Cancer Crusade is a citizen science game in which players design treatment strategies to influence a virtual tumor growth model. The treatment regimens that the players construct are collected and sent to an online database for analysis, which may give insights into clinically effective adaptive strategies. In parallel, a machine learning-based approach was applied to the game to find optimal treatment policies, and the optimized therapy approaches generated are compared to those generated by the human players. For the core game engine in Cancer Crusade, we started with a previously published hybrid cellular automata model of tumor metabolism and growth. The original model was used to study how tumor cells evolve acid-mediated invasion and the impact of treatment on these metabolic processes. We expanded the model by adding more drugs and cell phenotypes, including drug-resistant cells. The game was released on mobile platforms and has been generating data from plays for several years. The treatment strategies were analyzed using dendrogram clustering to find key decision differences and profile their relative performance. We also performed network analysis to observe treatment transitions. These analyses indicated several effective adaptive strategies, which tended to oscillate between chemotherapy and a pro-angiogenic drug, or chemotherapy and a hypoxia-activated prodrug, or combinations of all three of these drugs. These results parallel a machine learning (Q-learning) approach to the problem, which yielded a preferred strategy based on chemotherapy combined with a pro-angiogenic drug. The existence of several human-discovered alternative strategies suggests that in general human players may offer greater variety of successful strategies via citizen science games than Q-learning. The human and machine learning approaches also excelled in different areas. Human players tended to use less drug overall, and perform best on less aggressive tumors, while the Q-learning approach used more drug overall and performed best on more aggressive tumors. Citation Format: Rafael R. Bravo, Brenden K. Peterson, Mark Robertson-Tessi, Daniel M. Faissol, Alexander R.A. Anderson. Man vs machine: Crowdsourcing vs deep learning of adaptive therapy strategies [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B008.
Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity
Authors: Seongman Bae, Jae-Hoon Ko, Ju-Yeon Choi, Woo-Jung Park, So Yun Lim, Jin Young Ahn, Kyoung-Ho Song, Kyoung Hwa Lee, Young Goo Song, Yong Chan Kim, Yoon Soo Park, Won Suk Choi, Hye Won Jeong, Shin-Woo Kim, Ki Tae Kwon, Eun-Suk Kang, Ah-Ra Kim, Sundong Jang, Byoungguk Kim, Sung Soon Kim, Hee-Chang Jang, Jun Yong Choi, Sung-Han Kim, Kyong Ran Peck
Journal: Clinical Microbiology and Infection (2022)
Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality
Authors: Lars Björnebo, Tobias Nordström, Andrea Discacciati, Thorgerdur Palsdottir, Markus Aly, Henrik Grönberg, Martin Eklund, Anna Lantz
Journal: JAMA Oncology (2022)

Importance There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM). Objective To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa. Design, Setting, and Participants This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021. Exposures After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190). Main Outcomes and Measures Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM. Results The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; &gt;8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively). Conclusions and Relevance The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.
The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL
Authors: Kai Rejeski, Ariel Perez, Gloria Iacoboni, Olaf Penack, Veit Bücklein, Liv Jentzsch, Dimitrios Mougiakakos, Grace Johnson, Brian Arciola, Cecilia Carpio, Viktoria Blumenberg, Eva Hoster, Lars Bullinger, Frederick L Locke, Michael von Bergwelt-Baildon, Andreas Mackensen, Wolfgang Bethge, Pere Barba, Michael D Jain, Marion Subklewe
Journal: Journal for ImmunoTherapy of Cancer (2022)

<h3>Background</h3> CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) represents a promising treatment modality for an increasing number of B-cell malignancies. However, prolonged cytopenias and infections substantially contribute to the toxicity burden of CAR-T. The recently developed CAR-HEMATOTOX (HT) score—composed of five pre-lymphodepletion variables (eg, absolute neutrophil count, platelet count, hemoglobin, C-reactive protein, ferritin)—enables risk stratification of hematological toxicity. <h3>Methods</h3> In this multicenter retrospective analysis, we characterized early infection events (days 0–90) and clinical outcomes in 248 patients receiving standard-of-care CD19 CAR-T for relapsed/refractory large B-cell lymphoma. This included a derivation cohort (cohort A, 179 patients) and a second independent validation cohort (cohort B, 69 patients). Cumulative incidence curves were calculated for all-grade, grade ≥3, and specific infection subtypes. Clinical outcomes were studied via Kaplan-Meier estimates. <h3>Results</h3> In a multivariate analysis adjusted for other baseline features, the HT score identified patients at high risk for severe infections (adjusted HR 6.4, 95% CI 3.1 to 13.1). HT<sup>high</sup> patients more frequently developed severe infections (40% vs 8%, p&lt;0.0001)—particularly severe bacterial infections (27% vs 0.9%, p&lt;0.0001). Additionally, multivariate analysis of post-CAR-T factors revealed that infection risk was increased by prolonged neutropenia (≥14 days) and corticosteroid use (≥9 days), and decreased with fluoroquinolone prophylaxis. Antibacterial prophylaxis significantly reduced the likelihood of severe bacterial infections in HT<sup>high</sup> (16% vs 46%, p&lt;0.001), but not HT<sup>low</sup> patients (0% vs 2%, p=n.s.). Collectively, HT<sup>high</sup> patients experienced worse median progression-free (3.4 vs 12.6 months) and overall survival (9.1 months vs not-reached), and were hospitalized longer (median 20 vs 16 days). Severe infections represented the most common cause of non-relapse mortality after CAR-T and were associated with poor survival outcomes. A trend toward increased non-relapse mortality in HT<sup>high</sup> patients was observed (8.0% vs 3.7%, p=0.09). <h3>Conclusions</h3> These data demonstrate the utility of the HT score to risk-stratify patients for infectious complications and poor survival outcomes <i>prior</i> to CD19 CAR-T. High-risk patients likely benefit from anti-infective prophylaxis and should be closely monitored for potential infections and relapse.
Continuous Positive Airway Pressure for Cognition in Sleep Apnea and Mild Cognitive Impairment: A Pilot Randomized Crossover Clinical Trial
Authors: Camilla M. Hoyos, Nathan E. Cross, Zoe Terpening, Angela L. D’Rozario, Brendon J. Yee, Haley LaMonica, Nathaniel S. Marshall, Ronald R. Grunstein, Sharon L. Naismith
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Continuous Positive Airway Pressure for Cognition in Sleep Apnea and Mild Cognitive Impairment: A Pilot Randomized Crossover Clinical Trial." American Journal of Respiratory and Critical Care Medicine, 205(12), pp. 1479–1482
Is Regional Nodal Radiotherapy Necessary for Patients With cN1 and ypN0 Breast Cancer After Neoadjuvant Chemotherapy?—Reply
Authors: Andrea V. Barrio, Giacomo Montagna, Monica Morrow
Journal: JAMA Oncology (2022)

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Atypical B cells up-regulate costimulatory molecules during malaria and secrete antibodies with T follicular helper cell support
Authors: Christine S. Hopp, Jeff Skinner, Sarah L. Anzick, Christopher M. Tipton, Mary E. Peterson, Shanping Li, Safiatou Doumbo, Kassoum Kayentao, Aissata Ongoiba, Craig Martens, Boubacar Traore, Peter D. Crompton
Journal: Science Immunology (2022)

Several infectious and autoimmune diseases are associated with an expansion of CD21 − CD27 − atypical B cells (atBCs) that up-regulate inhibitory receptors and exhibit altered B cell receptor (BCR) signaling. The function of atBCs remains unclear, and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal flow cytometry analyses and RNA sequencing of Plasmodium falciparum ( Pf )–specific B cells isolated from study participants before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)–specific B cells as a comparator. At the healthy baseline before the malaria season, individuals had similar frequencies of Pf - and HA-specific atBCs that did not differ proportionally from atBCs within the total B cell population. BCR sequencing identified clonal relationships between Pf -specific atBCs, activated B cells (actBCs), and classical memory B cells (MBCs) and revealed comparable degrees of somatic hypermutation. At the healthy baseline, Pf -specific atBCs were transcriptionally distinct from Pf -specific actBCs and classical MBCs. In response to acute febrile malaria, Pf -specific atBCs and actBCs up-regulated similar intracellular signaling cascades. Pf -specific atBCs showed activation of pathways involved in differentiation into antibody-secreting cells and up-regulation of molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (T FH ) cells. In the presence of T FH cells and staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38 + antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens.
Abstract B015: Eco-evolutionary dynamics of poly-aneuploid cancer cells: A life history model
Authors: Anuraag Bukkuri, Kenneth J. Pienta, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown
Journal: Cancer Research (2022)

Abstract Despite major advances in cancer research over the last several decades, advanced cancers largely remain incurable due to the evolution of resistance. Recent experimental evidence suggests that a poly-aneuploid cancer cell (PACC) state may contribute to the emergence of therapeutic resistance by allowing cancer cells to avoid the effects of and adapt to extreme environmental stressors. The PACC state is enabled when aneuploid cells undergo whole genome doubling but subsequently bypass mitosis, cytokinesis, or both. We create a novel mathematical framework for modeling the eco-evolutionary dynamics of state-structured populations and use this framework to construct a model of cancer populations with an aneuploid and a PACC state. Using in silico simulations, we explore how the PACC state allows cancer cells to 1) survive extreme environmental conditions by exiting the cell cycle after S phase and protecting genomic material and 2) aid in adaptation to environmental stressors by increasing the cancer cell's evolvability (ability to generate heritable variation) through the increase in genomic content that accompanies polyploidization. In doing so, we demonstrate the ability of the PACC state to contribute to therapeutic resistance and stress the importance of targeting PACC populations for improved therapeutic outcomes. Citation Format: Anuraag Bukkuri, Kenneth J. Pienta, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown. Eco-evolutionary dynamics of poly-aneuploid cancer cells: A life history model [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B015.